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miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a

A single microRNA (miRNA) can regulate expression of multiple proteins, and expression of an individual protein may be controlled by numerous miRNAs. This regulatory pattern strongly suggests that synergistic effects of miRNAs play critical roles in regulating biological processes. miR-9 and miR-124...

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Autores principales: Xue, Qian, Yu, Caiyong, Wang, Yan, Liu, Ling, Zhang, Kun, Fang, Chao, Liu, Fangfang, Bian, Ganlan, Song, Bing, Yang, Angang, Ju, Gong, Wang, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879704/
https://www.ncbi.nlm.nih.gov/pubmed/27221778
http://dx.doi.org/10.1038/srep26781
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author Xue, Qian
Yu, Caiyong
Wang, Yan
Liu, Ling
Zhang, Kun
Fang, Chao
Liu, Fangfang
Bian, Ganlan
Song, Bing
Yang, Angang
Ju, Gong
Wang, Jian
author_facet Xue, Qian
Yu, Caiyong
Wang, Yan
Liu, Ling
Zhang, Kun
Fang, Chao
Liu, Fangfang
Bian, Ganlan
Song, Bing
Yang, Angang
Ju, Gong
Wang, Jian
author_sort Xue, Qian
collection PubMed
description A single microRNA (miRNA) can regulate expression of multiple proteins, and expression of an individual protein may be controlled by numerous miRNAs. This regulatory pattern strongly suggests that synergistic effects of miRNAs play critical roles in regulating biological processes. miR-9 and miR-124, two of the most abundant miRNAs in the mammalian nervous system, have important functions in neuronal development. In this study, we identified the small GTP-binding protein Rap2a as a common target of both miR-9 and miR-124. miR-9 and miR-124 together, but neither miRNA alone, strongly suppressed Rap2a, thereby promoting neuronal differentiation of neural stem cells (NSCs) and dendritic branching of differentiated neurons. Rap2a also diminished the dendritic complexity of mature neurons by decreasing the levels of pAKT and pGSK3β. Our results reveal a novel pathway in which miR-9 and miR-124 synergistically repress expression of Rap2a to sustain homeostatic dendritic complexity during neuronal development and maturation.
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spelling pubmed-48797042016-06-07 miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a Xue, Qian Yu, Caiyong Wang, Yan Liu, Ling Zhang, Kun Fang, Chao Liu, Fangfang Bian, Ganlan Song, Bing Yang, Angang Ju, Gong Wang, Jian Sci Rep Article A single microRNA (miRNA) can regulate expression of multiple proteins, and expression of an individual protein may be controlled by numerous miRNAs. This regulatory pattern strongly suggests that synergistic effects of miRNAs play critical roles in regulating biological processes. miR-9 and miR-124, two of the most abundant miRNAs in the mammalian nervous system, have important functions in neuronal development. In this study, we identified the small GTP-binding protein Rap2a as a common target of both miR-9 and miR-124. miR-9 and miR-124 together, but neither miRNA alone, strongly suppressed Rap2a, thereby promoting neuronal differentiation of neural stem cells (NSCs) and dendritic branching of differentiated neurons. Rap2a also diminished the dendritic complexity of mature neurons by decreasing the levels of pAKT and pGSK3β. Our results reveal a novel pathway in which miR-9 and miR-124 synergistically repress expression of Rap2a to sustain homeostatic dendritic complexity during neuronal development and maturation. Nature Publishing Group 2016-05-25 /pmc/articles/PMC4879704/ /pubmed/27221778 http://dx.doi.org/10.1038/srep26781 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Xue, Qian
Yu, Caiyong
Wang, Yan
Liu, Ling
Zhang, Kun
Fang, Chao
Liu, Fangfang
Bian, Ganlan
Song, Bing
Yang, Angang
Ju, Gong
Wang, Jian
miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a
title miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a
title_full miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a
title_fullStr miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a
title_full_unstemmed miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a
title_short miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a
title_sort mir-9 and mir-124 synergistically affect regulation of dendritic branching via the akt/gsk3β pathway by targeting rap2a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879704/
https://www.ncbi.nlm.nih.gov/pubmed/27221778
http://dx.doi.org/10.1038/srep26781
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